T3D0163 - 1,1,2-Trichloroethane

1. Cytokine receptor common subunit beta

High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.

1,1,2-Trichloroethane and its metabolites bind to DNA. (R717)

P32927

CSF2RB

SNPJam Report

• R717 — ATSDR - Agency for Toxic Substances and Disease Registry (1989). Toxicological profile for 1,1,2-trichloroethane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]

2. RNA

1,1,2-Trichloroethane and its metabolites bind to RNA. (R733)

RNA

• R733 — Mazzullo M, Colacci A, Grilli S, Prodi G, Arfellini G: 1,1,2-Trichloroethane: evidence of genotoxicity from short-term tests. Jpn J Cancer Res. 1986 Jun;77(6):532-9. [2426232 ]

3. Estrogen receptor

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)

P03372

ESR1

SNPJam Report

• S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.

4. Estrogen receptor beta

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)

Q92731

ESR2

SNPJam Report

• S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.